Neonates at risk of atopy show impaired production of interferon-gamma after stimulation with bacterial products (LPS and SEE).

Abstract

Recent studies demonstrate reduced interferon-gamma (IFN-gamma) secretion in neonates who became atopic later in life. The underlying pathomechanism is still unknown. We therefore examined the effects of bacterial products on neonatal IFN-gamma production acting through different T-cell- or antigen-presenting-cell (APC)-stimulating mechanisms: cord-blood mononuclear cells (CBMC) were incubated with lipopolysaccharide (LPS), staphylococcal enterotoxin E (SEE), or a combination of both and restimulated with PMA and ionomycin. LPS and SEE as single stimuli induced IFN-gamma production to the same extent in CBMC of neonates with high and low risk of atopy. In contrast, a combination of LPS and SEE had a multiplying effect on IFN-gamma secretion only in CBMC of neonates with low risk of atopy. Phenotype analysis revealed that only memory T cells showed impaired IFN-gamma synthesis (median 3.6% IFN-gamma-producing cells vs 14.2% in controls: P < 0.01), whereas IFN-gamma production by naive T cells did not differ in either group. Taken together, these results point to the existence of a disturbed function of costimulatory mechanisms in neonates at high risk of atopy, provoking reduced memory T-cell IFN-gamma production.